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Abstract：
Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-β signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.
摘要：
感染性骨缺损（IBDs）是骨科临床实践中的常见病。虽然手术和抗感染药物是首选的治疗方法，在许多情况下,抗感染治疗后，患者的骨愈合过程延长。淫羊藿-Curculigo草药对（ECP）已被证明对骨修复有效。然而,IBDs的ECP机制不足。在这项研究中,通过显微CT和组织学检查验证ECP在IBDs中的作用。对含ECP含药血清（ECP-CS）中的主要成分进行定性和定量分析。然后应用网络药理学方法来预测与骨修复相关的ECP的潜在途径。此外,通过分子生物学实验评估了ECP调节LncRNAMALAT1/miRNA-34a-5p/SMAD2信号轴的机制。体内实验表明，ECP可以显着促进骨修复。化学成分分析和途径鉴定的结果表明，TGF-β信号通路与ECP有关。体外实验结果表明，ECP-CS可以通过抑制LncRNAMALAT1和SMAD2的表达，提高miR-34a-5p的表达，从而逆转LPS引起的损伤，ALP,RUNX2和胶原A型在成骨细胞中表达显著。本研究表明ECP可以调节TGF-β/SMADs信号通路促进骨修复。同时,ECP可以通过调节IBD中LncRNAMALAT1/miRNA-34a-5p/SMAD2的信号轴减轻LPS诱导的骨丢失。
